The present invention relates to drug delivery devices and, in particular, it concerns a drug delivery device and corresponding methods which employ a pressurized reservoir of liquid medicament with controlled release via a flow restriction and multiple valves.
Low-dosage infusion pumps, both external and implantable, have been developed to the point of commercial and medical acceptance. For certain applications, a simple “constant flow” device is sufficient. In many cases, however, where patients require adjustments in the dosage as a function of time, constant flow pumps are inadequate. A typical example is diabetes where the quantity of medication, such as insulin, to be infused varies due to requirements of the patient. Fluctuations can occur on a daily basis or more randomly as a function of the ingestion of food. Consequently, to address the shortcomings of constant flow devices and obtain significant flexibility in dosage rates, various “implantable programmable” pumps have been developed. In the definition of system requirements dealing with such implantable programmable pumps, a device which will provide programmable bolus and basal flow rates over a wide dynamic range is a standing system requirement. This requirement can be set forth in a practical sense by reference to the treatment of diabetes. It is known that the amount of medication, typically insulin, to be infused per unit of time, should be adjusted at certain time intervals. A patient's requirements may fluctuate either at set, known rates or may vary abnormally, for example, by the ingestion of food or by other transitory conditions. Those conditions will call for the administration of a bolus dose of infusate. In the daily administration of insulin, however, the patient may require a basal dose that is supplanted by bolus doses at, for example, meal times. The difference in flow rates between basal and bolus doses may be quite large, in the orders of several times. Thus, a device to achieve proper flow rates over the spectrum of desired rates must have the ability to continuously infuse, at very low flow rates, yet provide, periodically, a substantially increased flow rate. Thus, the design criteria can be summarized as requiring, in the first instance, the ability for continuous basal drug delivery which is adjustable to varying choices of flow rate, including the ability to deliver a bolus dose at relatively high flow rates.
The requirements of programmability, wide range of flow rates, and failsafe operation greatly complicate the design of programmable drug delivery devices. Secondary issues such as power consumption, overall system life and economic viability limit the feasibility of many of the theoretical solutions that have been proposed to-date.
In an attempt to ensure failsafe operation, many programmable drug delivery devices employ a negative-pressure storage chamber, effectively precluding the possibility of drug leakage in the case of device malfunction. Examples of such devices, referred to as “negative pressure pumps”, may be found in U.S. Pat. Nos. 4,482,346 and 4,486,190. Both of these prior art devices are solenoid activated negative pressure pumps. A diaphragm storage chamber maintains the drug to be infused in a chamber having a diaphragm which separates the drug from propellant, normally freon, maintained at negative pressure. A solenoid is activated driving an armature and a bellows pumping element. This displacement of the armature opens a check valve which draws drug from the storage chamber into a downstream pumping chamber. A restriction will prevent backflow in the outlet during this short period. When the pump chamber is full, the check valve closes and the solenoid is then de-energized. A spring force typically displaces the bellows into the chamber pumping the drug through a restrictor and into the patient.
Negative pressure systems, while offering advantages of safety, suffer from major disadvantages. First, the negative pressure requirements require special precautions and equipment for filling and handling of the devices. Furthermore, since all of the drug must be positively displaced by a pump working against a pressure gradient, the devices have high power consumption, requiring bulky power sources and/or frequent battery replacement.
A second approach exemplified by U.S. Pat. Nos. 4,299,220 and 4,447,224 employs a positive pressure storage chamber in combination with an accumulator pump. The positive pressure of the storage chamber eliminates the handling problems of negative pressure devices. Where sufficiently high pressure is used to drive drug delivery without additional pumping, at least part of the power consumption is reduced, although many valve actuation elements are also consume a lot of power.
Despite the advantages of simplicity of implementation and energy efficiency, safety remains a major concern for positive pressure devices. Given the fact that drug chamber pressure is above body pressure, there remains a remote possibility for an overdose of drug should all valves in line with the output fail open at the same time. An improved degree of safety can be achieved in such systems by providing redundant valves. However, even with redundant valves, there remains some risk of multiple component failure which could result in overdosing. Depending upon the type of drug being administered, such overdosing could potentially be fatal.
A further problem associated with all types of programmable drug delivery devices is that of repeat usage. Throughout the field of medicine, there is a strong trend towards use of disposable components for infusion sets and the like. In the case of programmable drug delivery devices, the cost of the device is such that it is not presently feasible to produce single-use disposable devices. Furthermore, the subdivision of components between disposable “wet” components and reusable electronic and control components which is common in hospital infusion control systems such as the IVAC™ system is typically considered impractical here because of the extremely low flow rates and precision control required from such devices.
There is therefore a need for a programmable drug delivery device and corresponding methods of delivering drugs based upon a pressurized reservoir and which would reliably identify and appropriately address a range of malfunction conditions to avoid risk of drug overdosing. It would also be highly advantageous to provide a programmable drug delivery device and corresponding method facilitating subdivision of the device into reusable electronic and control components, and disposable components which come in contact with the drug. Finally, it would also be highly advantageous to provide a programmable drug delivery device which would have extremely low power consumption.